The focus of the renewal of the Training Program Connective Tissue and Regenerative Medicine (CTRM) is to provide doctoral students with advanced training in biomedical research. The didactic portion of the Program provides an integrated, innovative and rigorous educational experience that has as its goal the repair or regeneration of human tissues and organs and the preservation of the quality of human health. Resources for the program come from a core of well-funded faculty in several departments/divisions at Thomas Jefferson University and the Rothman Institute, as well as the Children's Hospital of Philadelphia. We request support for six predoctoral trainees. There are six program objectives: (1) to integrate contemporary advances in cell, molecular, and developmental biology towards understanding connective tissue function; (2) to relate fundamental advances in the life sciences to contemporary issues in musculoskeletal research regenerative medicine (3) to foster practical understandings of the pathophysiology of diseases of the skeleton; (4) to develop translational research by working closely with physicians in a clinical and surgical setting; (5) to implement translational research through interactions with scientists in the biotech industry and (6) to build a pipeline of talented individuals for careers n musculoskeletal research The didactic aspects of the training program are embedded in integrating developmental, cell and molecular biology; bioinformatics and functional genomics; tissue engineering and bioimaging; and translational medicine. So as to anchor the program in human disease, clinicians lecture in each of the major courses. By interacting frequently with surgeons who treat the ravages of disease, and by direct observation and discussion with faculty in the clinic and operating room, students develop an appreciation for health problems that are amenable to treatment by tissue engineering and regenerative medicine. Development of translational research is furthered by collaboration with scientists at local biotech companies and laboratories. Against this background, students develop their dissertation research which provides the foundation for their future careers as independent, innovative scientific investigators.